1. Field of the Invention
The present invention relates to a powder nebulization method and a powder nebulizer apparatus used in respiratory therapy and, in particular, to a continuously connected, continuous flow powder nebulizer useful in respiratory therapy to deliver powdered medications.
2. Description of the Related Art
Critically ill patients requiring mechanical ventilation are often victims of respiratory distress syndrome, status asthmaticus and pulmonary infections. Treatment of these and other severe respiratory conditions includes medications delivered directly to the lungs of the patient.
Respiratory delivery of medication for these conditions is preferable to oral, intravenous and subcutaneous delivery because it is non-invasive, permits rapid action of medicant, requires a relatively small dosage, is not filtered through the liver of the patient, and produces a low incidence of systemic side effects.
Nebulized or aerosolized solutions are the preferred method of respiratory delivery of medication; when fragmented into small particles, medicants are more efficiently deposited near sites of medicant activity in the lung.
Respiratory medications may be delivered to the lungs of the patient as an aerosol of a liquid or a powder. Clinical aerosols are currently generated by jet or ultrasonic nebulizers, metered dose inhalers (MDI) and dry powdered inhalers.
There are two types of nebulizers for the delivery of liquid medication to the lungs: jet nebulizers and ultrasonic nebulizers. In conventional jet nebulizers, compressed gas from a compressor or hospital air line is passed through a narrow constriction know as a jet. This creates an area of low pressure, and liquid medication from a reservoir is drawn up through a feed tube and fragmented into droplets by the airstream. Only the smallest drops leave the nebulizer directly, while the majority impact on baffles and walls and are returned to the reservoir. Consequently, jet nebulization takes several minutes to complete, depending upon the initial volume.
Important disadvantages of nebulizers include low lung deposition related to the use of tidal breathing. A substantial portion of the dose used in a jet nebulizer is retained permanently as a dead or residual volume on baffles and internal walls of the nebulizer chamber and cannot be released. Generally only 2-10% of the dose placed in the nebulizer ever reaches the lung. The consequences are a higher drug dosage and longer administrative time, along with the associated cost and risk of contamination.
The second type of aerosol generator is a metered dose inhaler (MDI), which delivers a bolus of more concentrated drug aerosols than the solution commonly available for nebulizers. For optimal effect, MDI delivery systems require proper administration technique, which includes coordinated actuation of aerosol delivery with inhalation, a slow inhalation of 0.5-0.75 liters per second, a deep breath approaching inspiratory capacity inhalation, and at least 4 seconds of breath holding.
Many patients find it difficult to properly administer medication with an MDI, especially during acute exorbation. An article which appeared in Eur. J. Respir. Dis., 68(5), 332 (1986), entitled "Bronchodilator Affects of a Fenoterol Meter Dose Inhaler and Fenoterol Powder in Asthmatics with Poor Inhaler Technique," described test findings showing that the effectiveness of bronchodilator medication, when delivered with an MDI, is dependent on good MDI technique. The article suggested that delivery of medication in a powdered form is more reliable for patients who do not exercise proper MDI technique.
MDI's can be equipped with devices that automatically couple actuation to inspiratory effort, thus eliminating the need for coordinating hand action with inhalation. Devices such as spacers and holding chambers also decrease partial velocity and reduce the number of large particles. Both of these features reduce oral pharyngeal and large airway deposition with a consequent reduction in systemic absorption. Deposition of aerosols from an MDI with a spacer or holding chamber is similar and perhaps better than the deposition of a properly used MDI alone.
Advantages of the MDI include deposition of 10-15% of the metered dose with consequent short treatment time, low cost and increased convenience. However, MDI's cannot be used by patients requiring mechanical ventilation. Other disadvantages include the need for patient cooperation, the practical limitations and inconveniences associated with increased dosing requirements due to the typically small dosages administered with an MDI, the limited number of currently available drugs, and the dependence on fluorocarbons for aerosol generation.
Others have recognized the need for new inhalation devices such as modified dry powder inhalers to replace use of MDI's due to environmental concerns related to the use of fluorocarbons. See "Today's Treatment of Airway Obstruction . . . and Tomorrow's?" Flenley, D. C., Respiration, 55 Suppl. 2, 4 (1989).
The third type of aerosol generator is a dry powdered inhaler. Dry powder inhalation devices currently in use include the inhalation devices commercially available under the trademarks "SPINHALER", "ROTAHALER", and "TURBOHALER", as well as the disc inhaler. Dry powder inhalers are breath actuated and usually require a higher inspiratory flow rate than that required for an MDI or a nebulizer. Flow rates of 1-2 liters per second are usually considered optimal, although flow rates as low as 0.5 liters per second may be effective for some dry powdered inhalers.
Advantages of dry powdered inhalers include relative ease of administration and the fact that they do not require fluorocarbon propellants. When a dry powdered inhaler is used properly, deposition appears to be similar to that of a properly used MDI.
However, powdered inhalers are limited by the dose they can provide and by the number of drugs currently available. Only terbutaline, salbutamol, dexamethasone and chromolyn sodium are available in powder form.
All conventional powder inhaler delivery systems utilize single dose capsules except the Turbuhaler for administration of terbutaline. While several devices have been developed which permit preloading of several single dose capsules, neither these devices nor the Turbuhaler have eliminated the other disadvantages of conventional powdered inhalers. See "A New Inhalation System for Bronchodilatation. Study of the Acceptance of the Ingelheim M Inhaler in Chronic Obstructive Respiratory Tract Diseases," Mutterlein, B. Schmidt, B., Fleisher, W., and Freund, E., Fortschr. Med., April 15, 108(11), 225 (1990); "In Vivo Evaluation of the New Multiple Dose Powder Inhaler and the Rotahaler Using the Gama Scintigraphy," Vidaren, M., Paronen, P., Vidaren, P., Vainir, P., and Nuutinen, J., Acta. Pharm. Nord., 2(1), 3 (1990); "Clinical Use of Dry Powder Systems," Crompton, G. K., Eur. J. Respir. Dis. Suppl., 122, 96 (1982).
Other disadvantages of dry powdered inhalers include the following: a) they are usually not particle size-selective and thus heavy oral pharyngeal deposition may occur; b) high humidity environments may cause clumping of the particles; and c) dry powdered inhalers cannot be used in ventilatory circuits.
Currently available devices for delivery of powdered medications in respiratory therapy do not employ nebulization technology.
The use of compressed air powered jet mills as a powder generator for inhalation experiments is disclosed in "Use of a Jet Mill for Disbursing Dry Powder for Inhalation Studies," Cheng, Y. S., Marshall, T. C., Henderson, R. R., and Newton, G. J., Am. Ind. Hya. Assoc. J., 46(8), 449 (1985). The jet mill consisted of an elongated channel, one material delivery jet, and two high speed air jets. Powder fed into the channel was disbursed by turbulence and centrifugal forces. The powder used in the inhalation experiments consisted of dye materials to be tested for toxicity. A flow rate of 400 liters per minute was maintained. The article does not address nebulization of powdered medication for purposes of respiratory therapy.
U.S. Pat. No. 4,232,002 discloses procedures for administering antihistamines. Methods disclosed include inhalation by a patient of mist, nebulized spray, or a cloud of fine solid particles. Products for delivery of medication include pressurized canister inhalers, portable dry powder insuffilators using capsules, and nebulizers. The only dry powder delivery system described is a dry powder inhaler using capsules of dry powder in single dose units. The delivery method described involves puncturing a capsule of dry powder medication which is disbursed by means of a turbomixer to be inhaled through a mouth piece. This patent does not address continuous flow or continuous delivery of inhalable medication. It does not enablingly teach or address jet nebulization of powdered solid medications, and does not teach a nebulizer vial which connects to a nebulizer to provide a device for introducing continuous flow.
U.S. Pat. No. 3,669,113 discloses a method and device for dispensing powdered medication from a perforated container by rotating the container by pneumatic means and causing the axis of rotation of the container to precess and describe a path of precession which is contained within a generally conical surface of a precession. The mechanisms described are based on varying shaft and bearing configurations. The method of this patent is said to be especially well suited to delivery of particles less than 80 microns in diameter. The patent does not address jet nebulization, continuous flow or continuous nebulization.
Recent developments in respiration therapy involve aerosolization and delivery of nebulized liquids on a continuous basis over several hours. Such delivery stabilizes the effects of the medication over time, reduces respiratory personnel support time, and reduces the chances of respiratory circuit contamination.
In our prior co-pending U.S. patent application Ser. No. 07/729,518, filed Jul. 12, 1991, a liquid nebulizer system is disclosed comprising a nebulizer attachable nebulizer vial, a large supply vessel, and a fluid delivery system, to be used with a conventional liquid nebulizer. The liquid nebulizer system provides for continuous delivery of liquid medication from a large supply vessel into the nebulizer vial which is attached to a conventional nebulizing apparatus, permitting continuous delivery of nebulized liquid medication. The disclosure of such prior copending application is hereby incorporated herein by reference.
It would be a significant advance in the art to combine the technology of nebulization systems with the efficiency of dry powdered inhaler systems.
Accordingly, it is an object of the present invention to provide a method and apparatus for continuous respiratory delivery of nebulized powdered medication.
It is another object of the invention to provide a method and apparatus for respiratory delivery of powdered medication which may be used in ventilatory circuits.
It is another object of the invention to provide a method and apparatus which overcome the disadvantages associated with currently available respiratory medicant delivery systems.
These and other objects and advantages of the present invention will be more fully apparent from the ensuing disclosure and appended claims.